Chapter Answers

1. Discuss the major recommendations for completing a family history and indicate the importance in helping to identify genetic disorders.

Answer: A family tree is the foundation for assessment of genetic disorders and it is important that this is documented clearly and accurately. The pattern of presentation enables the type of inheritance to be identified. With the specific signs and symptoms, and often additional clinical tests, the individual disease can usually be identified.

  • Obtain details about the patient/client followed by family members (parents, children, siblings)
  • Collect information about one side of the family and then the other side, as far as grandparents or further back if possible
  • Specifically find out about deceased relatives, including perinatal deaths
  • Include non-biologically related relatives (i.e. step-siblings, in-laws, adoptees) making the relationship clear on the pedigree
  • Ask about consanguinity (common in some cultures but not in others)
  • Private and sensitive information may be needed, e.g. pregnancies, including terminations, paternity
  • Separate family trees for different branches of the family will enable identification of shared information
  • Check whether there is any further information that may be useful. At each meeting check whether there have been any changes

2. Identify how screening is used in risk assessment in relation to genetic disorders, giving some examples of the approaches used for diagnosing different disorders.

Answer: The family history and a diagnosis enables risk assessment for the particular condition when three conditions are met: the diagnosis is certain; the mode of inheritance is understood; the biological relationship between the individuals concerned is known.

  • Prenatal diagnosis: aims to identify risk of a child with a genetic disorder being born and enable decision making about continuation of the pregnancy. Several approaches of visualisation, invasive techniques and genetic analysis can identify spina bifida, chromosomal abnormalities, skeletal disorders.
  • Post-natal screening: carried out shortly after birth on blood sample from a heel prick. A range of metabolic disorders (mostly rare) are tested for and many can be treated effectively if caught early, e.g. phenylketonuria, sickle cell disease.
  • Pre-symptomatic screening: suspected as result of family history, often occurring later in life. DNA examination enables diagnosis before symptoms develop, e.g. Huntington’s disease, and enables surveillance for changes.

3. Clarify the differences between autosomal and sex hormone aneuploidy, and give some examples from the two groups and their implications for quality of life.

Answer: Autosomal aneuploidy is when number of autosomes is abnormal. Incidence increases with maternal age. Monosomy is when one of pair is missing, trisomy is when three copies of a specific chromosome are present (e.g. Down syndrome – trisomy 21) and are more likely to be compatible with life. Sex hormone aneuploidy can include monosomies, trisomies and additional variations, most linked to increasing maternal age. The effects of these sex hormone aneuploidies are less severe and most are (at least sometimes) compatible with life. Turner syndrome is monosomy X.

4. What are the three factors which influence expression of an abnormal gene? Differentiate between the characteristics of dominant and recessive gene disorders and give some examples of each.

Answer: The expression of an abnormal gene is influenced by:

  • Germline mosaicism: more than one genetically different cell-line is present due to a mutation in the germline of one parent, but not in somatic cells.
  • Penetrance: relates to whether or not the disease carried in the abnormal gene results in presentation of the disorder. Can be reduced penetrance or age-dependent penetrance (presents later in life).
  • Variable expression: variation in degree of severity of presentation of condition due to environmental factors or other genes.

Condition occurs equally in either gender

Examples:

            Dominant:      Achondroplasia, Marfan syndrome, Huntingdon’s disease

            Recessive:       Cystic fibrosis, phenylketonuria, spinal muscular atrophy Dominant and recessive disorders vary as shown below:

Dominant

Recessive

 

 

One parent carries abnormal gene

Both parents carry abnormal gene

50% chance of occurrence in each pregnancy

1 in 4 chance of recurrence in each pregnancy

No skipping of generations. Vertical transmission of disease phenotypes

Clustering of disease around siblings. Vertical transmission not usually clear. Consanguinity increases risk

Either parent transmits condition to child

 

5. Differentiate between polygenic and multifactorial disorders. Discuss the importance of environmental factors in multifactorial chronic diseases.

Answer: Polygenic disorders occur as a result of a number of genes interacting. The traits concerned frequently show a continuous distribution pattern. Multifactorial conditions result from a combination of genetic changes and environmental factors. Multifactorial chronic conditions can be influenced by exercise, smoking, diet (including obesity), stress. Reducing these factors can minimise development of a number of these conditions.

6. Summarise your understanding of mitochondrial diseases and clarify how three-parent babies are created.

Answer: Mitochondria are essential for energy management for body function with several hundred mitochondria in each cell of the body. Each mitochondrion contains mitochondrial DNA, with the total mitochondrial DNA comprising a very small amount of the total DNA of the body. All the mitochondria and their DNA are from the ovum from the mother. The mutation rate of mitochondrial DNA is some 10 times greater than nuclear DNA and these mutations can result in severe diseases.

The formation of three-parent babies involves IVF with mitochondria from a healthy donor replacing those of the mother. These healthy infants can be produced by repair of the egg before fertilisation or by embryo repair.

7. Discuss the contribution of healthcare workers in working within genetic services.

Answer: Those working in genetic services provide genetic counselling to help patients and their families understand the disorder and are able to make informed decisions about future action. They may need to provide individualised support for those with a limited life span. The genetic team take on the coordinating role with different specialists whose intervention is needed by some with a rare complex condition. They also arrange genetic screening and maintain clinical registers to contact individuals for a new treatment or to provide appropriate support services. Confidentiality is one of the key ethical principles. Permission must always be obtained from the initial patient before telling others in the family. Practitioners are responsible for ensuring that their practice is evidence-based and may be collaborating with others in undertaking research.